Investigation of atherosclerotic plaques with MRI at 3 T using ultrasmall superparamagnetic particles of iron oxide

This study aims to investigate the uptake of the experimental ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agent DDM43/34 (Schering AG, Berlin, Germany) by aortic atherosclerotic plaques using magnetic resonance imaging (MRI) at 3 T. Six Watanabe heritable hyperlipidemic rabbits were injected with USPIO at doses of 0.1–1.0 mmol/kg Fe. Parasagittal magnetic resonance angiography (MRA) scans were acquired using 3D gradient-echo sequences before and after USPIO administration, then again after 6 h, 1 day, 2 days and 5 days. At later time points, when the USPIO concentration was too low to enhance blood signal, additional MRA scans were acquired during the infusion of gadopentate dimeglumine (Magnevist; Schering AG). In the images, widespread susceptibility artifacts demonstrated readily detectable USPIO uptake in the liver, bone marrow and lymphatic vessels. Surprisingly, however, no such effects could be associated specifically with the aortic vessel wall, in contrast to previous studies that showed strong uptake with similar pulse sequences. Histological analysis was performed on aortic slices from two animals, demonstrating that aortic plaques were active but showed very little USPIO uptake, consistent with MRI findings. We conclude that, despite the exciting potential of plaque detection using USPIO, some caution is advised since the absence of susceptibility effects does not necessarily imply the absence of plaque, even at 3 T, which offers increased sensitivity to susceptibility. Future work will investigate the dependence of such results on stage of plaque development, magnetic field strength and choice of contrast agent.     

Magnetic properties of novel superparamagnetic MRI contrast agents based on colloidal nanocrystals

Novel systems based on colloidal magnetic nanocrystals (NCs), potentially useful as superparamagnetic (SP) contrast agents for magnetic resonance imaging (MRI) have been investigated. The NCs we have studied comprise organic-capped single-crystalline maghemite (γ-Fe₂O₃) cores possessing controlled sizes and shapes. We have comparatively examined spherical and tetrapod-like NCs, the latter being branched particles possessing four arms which depart out at tetrahedral angles from a central point. The as-synthesized NCs are passivated by hydrophobic surfactant molecules and thus are fully dispersible in nonpolar media only. The NCs have been made soluble in aqueous solution by applying a procedure based on the surface intercalation and coating with an amphiphilic polymer shell. NMR relaxivities R₁ and R₂ were compared with ENDOREM^®, one of the standard commercial SP-MRI contrast agent. We found that the spherical NCs exhibit R₁ and R₂ relaxivities slightly lower than those of ENDOREM^®, over the whole frequency range; on the contrary, tetrapods show relaxivities about one order of magnitude lower. The physical origin of such difference in relaxivities between tetrapod- and spheres-based nanostructures is under investigation and it is possibly related to different sources of the magnetic anisotropy.     

Regional differences in rat brain displayed by fast MRI with superparamagnetic contrast agents

Gradient echo images of coronal sections through the brains of normal rats have been recorded at 2.0 T both before and at various times after intravenous bolus administrations of a superparamagnetic iron oxide suspension. The decrease in NMR signal due to the transit of the contrast agent has been quantified as a function of time. The image immediately following the injection can be subtracted from that pre-contrast to reveal regional differences related to blood flow.     

The oral administration of MnCl2: A potential alternative to IV injection for tissue contrast enhancement in magnetic resonance imaging

Mn⁺² (as MnCl₂) was administered to rabbits intravenously and orally (a route of administration which based upon our previous experiments in rats⁷ promises to give selective hepatobiliary enhancement with less systemic toxicity). Nuclear magnetic relaxation dispersion or T₁ (NMRD) was performed on selected tissues (heart, liver, kidney, serum, and bile) in both animal groups to examine possible qualitative and semiquantitative differences in T₁ relaxation at equivalent sacrifice times. One animal was given an oral dose of MnCl₂ (620 micromoles/kg) and imaged sequentially (T₁ weighted sequence, .12T) for 30 minutes. The NMRD curves for organ tissues show an increase in relaxation efficacy in the 10–20MHz range characteristic of Mn-macromolecular complexes and are similar irrespective of the route of administration. The lack of increased relaxation enhancement for bile in this frequency range reflects cleavage of this complex upon excretion. Decreased overall relaxation in the liver is observed when oral Mn⁺² is compared to IV Mn⁺² due to the small fraction of administered dose that is absorbed. However, the images document a significant increase in the intensity of liver signal after the oral dose. We suspect this dose may ultimately be adjusted downward to give selective hepatobiliary effects.     

Structural effect on degradability and in vivo contrast enhancement of polydisulfide Gd(III) complexes as biodegradable macromolecular MRI contrast agents

The structural effect of biodegradable macromolecular magnetic resonance imaging (MRI) contrast agents, polydisulfide gadolinium (Gd)(III) chelates, on their in vitro degradability, and cardiovascular and tumor imaging were evaluated in mice. Polydisulfide Gd(III) chelates, Gd-DTPA cystamine copolymers (GDCC), Gd-DTPA l-cystine copolymers (GDCP), Gd-DTPA d-cystine copolymers (dGDCP) and Gd-DTPA glutathione (oxidized) copolymers (GDGP), with different sizes and narrow molecular weight distribution were prepared and evaluated both in vitro and in vivo in mice bearing MDA-MB-231 tumor xenografts. GDGP with large steric hindrance around the disulfide bonds had greater T(1) and T(2) relaxivities than GDCC, GDCP and dGDCP. The degradability of the polydisulfide by the endogenous thiols decreased with increasing steric effects around the disulfide bonds in the order of GDCC>GDCP, dGDCP>GDGP. The size and degradability of the contrast agents had a significant impact on vascular contrast enhancement kinetics. The agents with a large size and low degradability resulted in more prolonged vascular enhancement than the agents with a small size and high degradability. It seems that the size and degradability of the agents did not significantly affect tumor enhancement. All agents resulted in significant contrast enhancement in tumor tissue. This study has demonstrated that the vascular enhancement kinetics of the polydisulfide MRI contrast agents can be controlled by their sizes and structures. The polydisulfide Gd(III) chelates are promising biodegradable macromolecular MRI contrast agents for magnetic resonance angiography and cancer imaging.     

Magnetic and relaxometric properties of polyethylenimine-coated superparamagnetic MRI contrast agents

Novel systems to be employed as superparamagnetic contrast agents (CA) for magnetic resonance imaging (MRI) have been synthesized. These compounds are composed of an iron oxide magnetic core coated by polyethylenimine (PEI) or carboxylated polyethylenimine (PEI-COOH). The aim of the present work was to prepare and study new nanostructured systems (with better or at least comparable relaxivities, R₁ and R₂, with respect to the commercial ones) with controlled, almost monodisperse average dimensions and shape, as candidates for molecular targeting. By means of atomic force microscopy (AFM) measurements we determined the average diameter, of the order of 200 nm, and the shape of the particles. The superparamagnetic behavior was assessed by SQUID measurements. From X-ray data the estimated average diameters of the magnetic cores were found to be 5.8 nm for PEI-COOH60 and 20 nm for the compound named PEI25. By NMR-dispersion (NMRD), we found that PEI-COOH60 presents R₁ and R₂ relaxivities slightly lower than Endorem^®. The experimental results suggest that these novel compounds can be used as MRI CA.     

Superparamagnetic iron oxide particles and positive enhancement for myocardial perfusion studies assessed by subsecond T1-weighted MRI

Superparamagnetic iron oxide particles (SPIOs) are usually referred to as T₂ MR contrast agents, reducing signal intensity (SI) on T₂-weighted MR images (negative enhancement). This study reports the original use of SPIOs as T₁-enhancing contrast agents, primarily assessed in vitro, and then applied to an in vivo investigation of a myocardial perfusion defect. Using a strongly T₁-weighted subsecond MR sequence with SPIOs intravenous (IV) bolus injection, MR imaging of myocardial vascularization after reperfusion was performed, on a dog model of coronary occlusion followed by reperfusion. Immediately after the intravenous bolus injection of 20 μmol/kg of SPIOs, a positive signal intensity enhancement was observed respectively, in the right and left ventricular cavity and in the nonischemic left myocardium. Moreover, compared to normal myocardium, the remaining ischemic myocardial region (anterior wall of the left ventricle) appeared as a lower and delayed SI enhancing area (cold spot). Mean peak SIE in the nonischemic myocardium (posterior wall) was significantly higher than in the ischemic myocardium (anterior wall) (110 ± 23% vs. 74 ± 22%, Mann-Whitney test < 1%, n₁ = 6, n₂ − n₁ = 0, U > 2). In conclusion, the T₁ effect of SPIOs at low dose, during their first intravascular distribution, suggests their potential use as positive markers to investigate the regional myocardial blood flow and some perfusion defects such as the “no-reflow phenomenon”.     

连续照明时成像对比度与气象条件的关系

 通过同轴激光连续照明成像模型分析了大气后向散射对成像对比度的影响，得出了考虑散射因素时成像对比度的计算公式。基于不同气象条件下大气粒子散射特点，讨论了霾和雾两种不同天气时成像对比度随照明距离的变化规律，并与实验结果进行了对比，计算结果与实验吻合较好。     

Magnetic resonance imaging with superparamagnetic iron oxide particles for the detection of myocardial reperfusion

The effect of superparamagnetic iron oxide particles on magnetic resonance myocardial signal intensity was examined in order to define the ability of this agent to identify normal, ischemic, and reperfused myocardium. Data were obtained from 6 normal rats (group 1) and from 6 heterotopic isogenic rat heart transplants (group 2) at 4.7 T with a multislice spin-echo sequence. Images were acquired in (a) normal rats before and after the infusion of 36 μmol Fe/kg of AMI-25 (group 1) and (b) rat heart transplants during control, global myocardial ischemia (before and after the injection of 72 μmol Fe/kg of AMI-25), and following reperfusion (group 2). Myocardial signal intensity decreased by 36 ± 4%, p < 0.001, following contrast infusion in normal hearts (group 1). The intensity remained constant in the rat heart transplants (group 2) during coronary occlusion, both before and after the infusion of AMI-25 and decreased by 61 ± 7%, p < 0.001, upon reperfusion. The larger effect of AMI-25 in reperfused as compared to normal myocardium suggests the presence of ischemia-induced hyperemia. There was no significant difference (analysis of variance) among intensities from different myocardial regions in either group at any stage of the experiment. We conclude that the use of AMI-25 permits identification of normal, ischemic, and reperfused myocardium and may therefore be helpful for the early detection of reperfusion following thrombolytic therapy for acute myocardial infarction.     

Changes in MR signal intensity and contrast enhancement of therapeutically irradiated soft tissue

Increased MR signal intensity was observed on T₂-weighted, STIR, and Gadolinium-DTPA-enhanced T₁-weighted images of subcutaneous and muscular soft tissue in 9 of 10 children treated with combination chemotheraphy and radiation therapy (RT) for malignancy in the pelvis or an extremity. Total radiation doses ranged from 59.5 to 65 Gy. Eight of the patients with these changes received hyperfractionated RT (seven for Ewing sarcoma and one for perineal rhabdomyosarcoma); one was treated for pelvic hemangiopericytoma with once-daily fractions. Evidence of soft tissue damage became apparent as early as the sixth week of RT and was seen for up to 69 wk post-RT. There was no clear MR evidence of RT-induced soft tissue damage in one patient, who underwent hyperfractionated RT for pelvic rhabdomyosarcoma. Other MR findings in this group included evidence of bladder wall thickening in three of the seven patients given pelvic RT and increased T₁-weighted signal of irradiated marrow in nine patients. All patients had clinical evidence of skin, soft tissue, or epithelial radiation effects. Increased MR signal intensity secondary to RT-induced damage can be differentiated from widespread tumor by geometric borders that conform to the margins of the radiation field.     

The gadolinium complexes with polyoxometalates as potential MRI contrast agents

The two gadolinium (Gd) polyoxometalates, K(15)[Gd(BW(11)O(39))(2)] [Gd(BW(11))(2)] and K(17)[Gd(CuW(11)O(39))(2)] [Gd(CuW(11))(2)] have been evaluated by in vivo and in vitro experiments as the candidates of potential tissue-specific magnetic resonance imaging (MRI) contrast agents. T(1) relaxivities of 17.12 mM(-1) x s(-1) for Gd(BW(11))(2) and 19.95 mM(-1) x s(-1) for Gd(CuW(11))(2) (400 MHz, 25 degrees C) were much higher than that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in bovine serum albumin and human serum transferrin solutions were also reported. After administration of Gd(BW(11))(2) and Gd(CuW(11))(2) to Wistar rats, MRI showed longer and remarkable enhancement in rat liver and favorable renal excretion capability. The signal intensity increased by 37.63+/-3.45% for the liver during the whole imaging period (100 min) and by 61.47+/-10.03% for kidney within 5-40 min after injection at 40+/-1-micromol x kg(-1) dose for Gd(CuW(11))(2), and Gd(BW(11))(2) induced 50.44+/-3.51% enhancement in the liver in 5-50-min range and 61.47+/-10.03% enhancement for kidney within 5-40 min after injection at 39+/-4 micromol x kg(-1) dose. In vitro and in vivo study showed that Gd(BW(11))(2) and Gd(CuW(11))(2) are favorable candidates as tissue-specific contrast agents for MRI.     

Simulation study of ghost image phenomenon induced by contrast enhancement film in plasma display panels

We have performed simulations of the ghost image phenomenon induced by a contrast enhancement film used for plasma display panels (PDPs). An optical imaging system was designed in order to investigate the ghost image qualitatively and quantitatively. We report on and discuss the effects of the material parameters and film orientation on the relative illuminance of the ghost image for a conventional louver-type contrast enhancement film adopting a trapezoidal black-stripe structure. The ghost image phenomenon is strongly affected by the film orientation relative to the PDP module and the difference between the refractive index of the ultraviolet curable urethane acrylate layer and that of the black stripes. We show that when the top side of the black stripes faces the PDP module and the refractive index difference is small, the ghost image phenomenon is weakened.     

Gadolinium oxide: a protoype agent for contrast enhanced imaging of the liver and spleen with magnetic resonance

Gd2O3 particles (less than 2 microns) in suspension were evaluated as a potential contrast agent for liver-spleen imaging with magnetic resonance. The agent was administered IV to rabbits in doses ranging from 10 to 120 mumol/kg and the tissues removed after sacrifice for in vitro T1 and T2 analysis. The temporal response was determined in liver and spleen samples of rabbits given a fixed dose (60 mumol/kg) and sacrificed at intervals from 15 min to 60 hr later. Documentation of the subanatomic location of Gd2O3 particles in tissue was accomplished by electron microscopy and x-ray dispersion microanalysis. T1 weighted images were obtained at 0.12T on a prototype resistive scanner. The liver, spleen, and lung relaxation times are very responsive to Gd2O3 IV and the effect is dose related. A peak effect is observed between 3-7 hr after injection and relaxation times may normalize by 60 hr. By electron microscopic and x-ray analysis, Gd2O3 is most prominently found in the hepatic and splenic sinusoids. The images show marked enhancement of liver and splenic tissues, aiding in the clear delineation of these tissues from neighboring structures.     

T2 relaxation induced by clusters of superparamagnetic nanoparticles: Monte Carlo simulations

Clustering strongly affects the transverse (T2) relaxation induced by superparamagnetic nanoparticles in magnetic resonance experiments. In this study, we used Monte Carlo simulations to investigate systematically the relationship between T2 values and the geometric parameters of nanoparticle clusters. We computed relaxation as a function of particle size, number of particles per cluster, interparticle distance, and cluster shape (compact vs. linear). We found that compact clusters induced relaxation equivalent to similarly sized single particles. For small particles, the shape and density of clusters had a significant effect on T2. In contrast, for larger particles, T2 relaxation was relatively independent of cluster geometry until interparticle distances within a cluster exceeded ten times the particle diameter. Results from our simulations suggest principles for the design of nanoparticle aggregation-based sensors for MRI.     

Accuracy and stability of measuring GABA, glutamate, and glutamine by proton magnetic resonance spectroscopy: a phantom study at 4 Tesla

Proton magnetic resonance spectroscopy has the potential to provide valuable information about alterations in gamma-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln) in psychiatric and neurological disorders. In order to use this technique effectively, it is important to establish the accuracy and reproducibility of the methodology. In this study, phantoms with known metabolite concentrations were used to compare the accuracy of 2D J-resolved MRS, single-echo 30 ms PRESS, and GABA-edited MEGA-PRESS for measuring all three aforementioned neurochemicals simultaneously. The phantoms included metabolite concentrations above and below the physiological range and scans were performed at baseline, 1 week, and 1 month time-points. For GABA measurement, MEGA-PRESS proved optimal with a measured-to-target correlation of R(2)=0.999, with J-resolved providing R(2)=0.973 for GABA. All three methods proved effective in measuring Glu with R(2)=0.987 (30 ms PRESS), R(2)=0.996 (J-resolved) and R(2)=0.910 (MEGA-PRESS). J-resolved and MEGA-PRESS yielded good results for Gln measures with respective R(2)=0.855 (J-resolved) and R(2)=0.815 (MEGA-PRESS). The 30 ms PRESS method proved ineffective in measuring GABA and Gln. When measurement stability at in vivo concentration was assessed as a function of varying spectral quality, J-resolved proved the most stable and immune to signal-to-noise and linewidth fluctuation compared to MEGA-PRESS and 30 ms PRESS.     

Gd complexes of diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide as a new liver-specific MRI contrast agent

This study was to describe the synthesis of complexes of gadolinium diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide Gd-DTPA-CSn (n = 6, 8, 11) as a new class of contrast agent as well as its magnetic property in a pilot magnetic resonance imaging. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r₁), FLASH imaging in phantoms in vitro and signal intensity in vivo of the rat abdominal axial imaging. The r₁ of Gd-DTPA-CS₁₁ was up to 11.65 mM^− 1·s^− 1, which was 3 times higher than that of the analogous MRI contrast agent Gd-DTPA in commercial use. In vivo MR images of rat obtained with Gd-DTPA-CS₁₁ showed strong signal enhancement in liver and the vessels of the liver parenchyma during the extended period of time. The present study suggests that the new synthesized gadolinium complexes can be used as a new class of practical liver-specific MRI contrast agent because of its superior performance compared with Gd-DTPA.     

The effects of iron oxides on proton relaxivity

The magnetic properties and relaxivities of superparamagnetic, ferromagnetic and paramagnetic iron oxides are presented and compared. The iron in colloids of ferromagnetic iron oxide has a large spin-spin relaxivity and a small spin-lattice relaxivity. The iron in colloids of paramagnetic iron oxide has a low spin-spin and spin-lattice relaxivity. The iron in colloids of highly dispersed superparamagnetic iron oxides has a large spin-spin relaxivity and a large spin-lattice relaxivity. Superparamagnetic colloids with various particle sizes in solution have been made by varying the number of superparamagnetic iron oxide crystals per particles in solution. Superparamagnetic colloids of larger solution particle size have a lower spin-lattice relaxivity than colloids comprised of smaller solution particle sizes.     

HCC-to-liver contrast on arterial-dominant phase images of EOB-enhanced MRI: comparison with dynamic CT

The purpose of this study was to assess the efficacy of arterial-dominant phase images of gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid (EOB)-enhanced magnetic resonance imaging (MRI) for evaluation of arterial blood supply in hepatocellular carcinoma (HCC) in comparison with that of multiphasic dynamic computed tomography (CT). This study comprised 30 patients (22 men and 8 women, mean age: 68.0 years) with 40 pathologically proven HCCs (well differentiated: 3, moderately differentiated: 30, poorly differentiated: 7, mean diameter: 45.1 mm), all of whom underwent EOB-enhanced MRI and dynamic CT preoperative assessment. Regions of interest were placed over HCCs and the adjacent normal liver, and signal intensities or CT values were measured by two experienced abdominal radiologists on the arterial-dominant phase images of EOB-enhanced MRI and dynamic CT images. HCC-to-liver contrasts [Michelson's contrast: C_M=(S_HCC− S_Liver)/(S_HCC+ S_Liver)] were calculated and compared among the modalities. HCC-to-liver contrasts were also visually scored on a 5-point scale and compared. The mean C_M and visual score for dynamic CT were significantly higher than those for EOB-enhanced MRI. Good agreements were obtained among the two observers. Dynamic CT is a more suitable modality than EOB-enhanced MRI for evaluation of arterial blood supply in HCC. This should be taken into account for diagnosis and management of HCC.     

Comparative analysis of the 1H NMR relaxation enhancement produced by iron oxide and core-shell iron-iron oxide nanoparticles

Physicochemical and magnetorelaxometric characterization of the colloidal suspensions consisting of Fe-based nanoparticles coated with dextran have been carried out. Iron oxide and iron core/iron oxide shell nanoparticles were obtained by laser-induced pyrolysis of Fe(CO)₅ vapours. Under different magnetic field strengths, the colloidal suspension formed by iron oxide nanoparticles showed longitudinal (R₁) and transverse (R₂) nuclear magnetic relaxation suspension (NMRD) profiles, similar to those previously reported for other commercial magnetic resonance imaging (MRI) contrast agents. However, colloidal suspension formed by ferromagnetic iron-core nanoparticles showed a strong increase of the R₁ values at low applied magnetic fields and a strong increase of the R₂ measured at high applied magnetic field. This behaviour was explained considering the larger magnetic aggregate size and saturation magnetization values measured for this sample, 92 nm and 31 emu/g Fe, respectively, with respect to those measured for the colloidal suspensions of iron oxide nanoparticles (61 nm and 23 emu/g Fe). This suspension can be used both as T₁ and T₂ contrast agent.